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Although bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are widely recognized as promising therapeutic agents, the age‐related impacts on cellular function remain largely uncharacterized. In this study, we found that BM‐MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts ( p  &lt; .001). Given this significant healing advantage, we then used single‐cell transcriptomic analysis to provide potential molecular insights into these observations. We found that the young cells contained a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration. In addition, we identified a unique, quiescent subpopulation that was exclusively present in young donor cells. Together, these findings may explain a novel mechanism for the enhanced healing capacity of young stem cells and may have implications for autologous cell therapy in the extremes of age. S tem  C ells   2019;37:240–246

Single‐Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age‐Related Cellular Subpopulation Depletion and Impaired Regenerative Function